There are many factors which have been adjudged involved in atherosclerosis and this complexity has made definitive studies of this disease extremely difficult. The proposed research takes advantage of the unique opportunity provided in this Department to simultaneously investigate atherogenesis in given subhuman primates both in vivo and in vitro. Our large Subhuman Primate Core Facility has a productive breeding unit and many ongoing experiments are probing the development of atheromata in infant monkeys maintained on different dietary regimens. These same animals which will be subject to full biochemical, physiological, and pathological studies, will also be the source of the blood vessel smooth muscle cells to be used in the proposed work. Smooth muscle cells will be cultivated in vitro from major arteries of squirrel and cebus monkeys and their uptake and metabolism of lipids will be studied. Cells will be obtained from the aortic arch and abdominal aorta in the squirrel monkey which represent areas of high and low atherosclerosis susceptibility, respectively. Similarly, cells will be taken from the aorta and the carotid artery near its bifurcation in the cebus monkey because these represent areas of high susceptibility in this species. All of these cells will be tested under carefully controlled conditions for their repsonse to different exogenous lipids (including cholesterol, cholesteryl esters, acyl-glycerides, unesterified fatty acids) and to sera from monkeys being fed control or atherogenic diets. Effects of age, sex, species, individual variation within a species, and serum lipid composition will be examined. By determining the extent to which any of these as well as the anatomical site from which the cells were derived is of importance to lipid accumulation and metabolism, it may be possible to establish biochemical and pathological correlations of atherogenesis in vitro and in vivo.